The regulation of enzyme synthesis in developing mammals and in adults with cancer is the broad subject of this research. Studies of normal ontogeny in fetal and perinatal rats will be concerned with physiological stimuli of selective gene expression, especially with the role of cortisol and thyroxine in hepatic differentiation. The opposite process, the partial undifferentiation of the pattern of enzymes and isozymes is the phenomenon to be investigated in the liver of adult rats with extrahepatic tumors. We plan to elucidate the nature and mode of action of systemic factors through which neoplasms exert their effects of anatomically distant tissues. This should provide new insight into the progressive deterioration of metabolic functions in the organism of cancer subjects. In addition, biochemical changes in the histologically normal liver, which are detectable before the distant tumors are palpable, may reveal the presence of latent neoplasms in the organism. We thus plan to identify such specific enzymic abnormalities, and show that they revert to normal upon complete surgical eradication of the tumors but not if regrowth occurs. Studies of the effects of the blood of host rats on cell differentiation in vitro may lead to noninvasive methods for the diagnosis of cancer, as well as serve to elucidate molecular mechanisms underlying the host syndrome.